Conifer Translational Genomics Network

Coordinated Agricultural Project

Genomics in Tree Breeding and

Forest Ecosystem Management
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Module 3 – Population Genetics
Nicholas Wheeler & David Harry – Oregon State University

www.pinegenome.org/ctgn
 Population genetics
 Population genetics is the
study of genetic differences
within and among populations
of individuals, and how these
differences change across
generations

 In the classic view, it is the

study of the amount and
distribution of genetic variation
in populations and species,
and how it got that way

 Population genetics describes

the mechanics of how
evolution takes place
Image Credit: Nicholas Wheeler, Oregon State University
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 Why study genes in populations?
 In natural populations:
– Adaptation – the ability to survive and exploit an environmental niche –
involves the response of populations, not individuals

 In breeding populations:
– Genetic gain – improving the average performance of populations for
desired breeding objectives – depends on selecting and breeding
parents with the best genetic potential

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 Population genetics addresses many topics

 How genetically diverse is a species or population?

– Contrast diversity in populations that differ in life-history traits, pop size,
breeding structure, etc

 Are different populations closely related to one another?

– Monitor diversity for conservation purposes

 What is the potential for inbreeding depression?

– What is the minimum viable population size from a genetic standpoint?

 How is genetic variation maintained?

 Which genes/alleles are responsible for phenotypic variation?

 How are species related (phylogenetics) and how did they acquire
their current distribution (biogeography)?

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 What do population geneticists typically
measure?
Typical descriptive statistics Allele Frequency
A1 0.2
Locus ‘X’ in pop #1 A2 0.5
A3 0.3
Total = 1.0

Genotype Frequency
A1 A1 0.1
A1 A2 0.1
A1 A3 0.1
A2 A2 0.3
A2 A3 0.3
A3 A3 0.1
Sum = 1.0
A (# alleles) = 3
Ho (observed heterozygosity) = 0.5
With data from more loci, you an also calculate,
P (% polymorphic loci) = % of loci with >1 allele
Figure Credit: Glenn Howe, Oregon State University

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 The Hardy-Weinberg principle
 The frequencies of alleles and genotypes in a population will
remain constant over time (given certain assumptions which
describe a static, or non-evolving population)

 The frequencies of alleles and genotypes can be described

mathematically, where p and q are the frequencies of the alleles A1
and A2

Freq. A1A1 homozygote Freq. A2A2 homozygote

2 2
p + 2pq + q = 1.0
Freq. A1A2 heterozygote

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 Random mating restores HW proportions
each generation

Figure Credit: White, T. L, W. T. Adams, and D. B. Neale. 2007. Forest genetics. CAB International, Wallingford, United Kingdom. Used with permission.

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 HW equilibrium conditions
 For Hardy-Weinberg equilibrium to exist, a number of assumptions
must be met. For instance, the population under consideration must
– Be random mating (translation = all possible pairings of mates are
equally likely)
– Be infinitely large (translation = sampling with replacement)
– Have no selection (which biases genotype frequencies)
– Have no migration (since all alleles must be sampled from the same
pool)
– Have no mutation (which introduces new variants)

 Obviously, such “ideal” populations rarely (if ever) exist

 Still, minor violations of assumptions generally have little impact

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 HW : Non-random mating
When individual genotypes do not mate randomly, HW equilibrium
proportions are not observed among the offspring

 We’ll look at two kinds of non-random mating

– Population substructure/admixture
– Inbreeding (mating among related individuals)

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 HW : Population admixture
 Consider mixing individuals
from non-interbreeding
subpopulations (e.g. alligator
lizards from Washington and
Idaho)

 Even if each subpopulation is

in HW, the admixed group is
not (p1 ≠ p2)

 The admixed group will

appear to have too many
homozygotes

 This situation is called the

Wahlund effect
Figure Credit: Hartl. 2000. A primer of population genetics. Used with permission of Sinauer Associates.

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 Population structure: Wahlund’s effect
 Wahlund’s effect: As long as allele frequencies vary among
subpopulations, even if each subpopulation exhibits HW
proportions, then more homozygotes will be observed than would
be expected based on the allele frequency of the metapopulation

 The relative increase in homozygosity is proportional to the

variance in allele frequencies among subpopulations, as measured
by F (where 0 ≤ F ≤ 1)

 F is commonly known as Wright’s fixation index and may be most

simply interpreted as F = 1 – (Hobs / Hexp ), where the values
represent observed and expected levels of heterozygosity

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 Inbreeding
 Inbreeding (mating among relatives) increases homozygosity
relative to HW
– Rate is proportional to degree of relationship
– Distant cousin < first cousin < half-sib < full-sib < self

 Recurrent inbreeding leads to a build-up of homozygosity, and a

corresponding reduction in heterozygosity

 Inbreeding affects genotype frequencies, but not allele frequencies

 How does inbreeding affect deleterious recessive alleles?

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 Inbreeding and homozygosity

 F reflects a proportional reduction in heterozygosity, and a build-up

of genetic relatedness. HW implies F = 0. With recurrent selfing, F
goes to 1
Figure Credit: White, T. L, W. T. Adams, and D. B. Neale. 2007. Forest genetics. CAB International, Wallingford, United Kingdom. Used with permission. (Table 5.1 in Falconer and Mackay, 1996)

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 Inbreeding depression
 Inbreeding often leads to
reduced vitality (growth,
fitness)

 Deleterious recessive alleles

are made homozygous

 Outcrossing species are more

likely to suffer higher
inbreeding depression

Image Credit: White, T. L, W. T. Adams, and D. B. Neale. 2007. Forest genetics. CAB International, Wallingford, United Kingdom. Used with permission.
(Photo courtesy of F. Sorensen, USFS, Pacific Northwest Research Station)

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 Evolutionary forces change allele frequencies

 Mutation  a random heritable change in the genetic material

(DNA) – ultimate source of all new alleles

 Migration (gene flow)  the introduction of new alleles into a

population via seeds, pollen, or vegetative propagules

 Random genetic drift  the random process whereby some alleles

are not included in the next generation by chance alone

 Natural selection  the differential, non-random reproductive

success of individuals that differ in hereditary characteristics

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 Mutation
 Mutations are the ultimate source of genetic variation on which
other evolutionary forces act (e.g. natural selection)

 Mutations at any one locus are rare, but with sufficient time,
cumulative effects can be large

 Heritable changes in DNA sequence alter allele frequencies as

new alleles are formed

 Effects on populations – Mutations promote differentiation (but

effects are gradual in the absence of other evolutionary forces)

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 Gene flow: Migration of alleles
 Gene flow – the movement of
alleles among populations

 Movement may occur by

individuals (via seed) or
gametes (via pollen) between
populations Seed
(low gene flow)
 Effects on populations – Pollen
(high gene flow)
gene flow hinders
differentiation. It is a
cohesive force which tends to
bind populations together

Image Credit: Glenn Howe, Oregon State University

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 Migration rates
 Modest migration rates will
prevent divergence of
populations

 The absolute number of

migrants per generation
affects Fst, the fixation index,
independent of subpopulation
size

Figure Credit: Hartl. 2000. A primer of population genetics. Used with permission of Sinauer Associates.

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 Genetic drift
 Drift reflects sampling in small
populations. Subgroups follow
independent paths. Allele
frequencies will vary among
subgroups while frequencies in
the metapopulation remain
relatively stable. Major impacts of
drift are:

 Reduced genetic diversity (loss of

alleles.

 Reduced average heterozygosity.

 Increased genetic differentiation

among populations.
Figure Credit: Modified from White et al. Forest Genetics. 2007. Fig. 5.10

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 Random genetic drift: Bottlenecks
 Bottleneck effect: A type of
genetic drift that occurs when
a population is severely
reduced in size such that the
surviving population is no
longer genetically
representative of the original
population

Figure credit: Nicholas Wheeler, Oregon State University

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 Natural selection
 Natural selection  First proposed by Charles Darwin in mid-
1800s. The differential reproductive success of individuals that
differ in hereditary characteristics
– Not all offspring survive and reproduce
– Some individuals produce more offspring than others (mortality,
disease, bad luck, etc)
– Offspring differ in hereditary characteristics affecting their survival
(genotype and reproduction are correlated)
– Individuals that reproduce pass along their hereditary characteristics to
the next generation
– Favorable characteristics become more frequent in successive
generations

 Effects on populations:
– Promotes differentiation between populations that inhabit dissimilar
environments
– Hinders differentiation between populations that inhabit similar
environments

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 Relative fitness: Key considerations
 Which genotype has the largest relative fitness?
– Determines the direction in which allele frequencies will change

 Are fitness differences large or small?

– Determines rate of change over generations – fast or slow

 What is the fitness of the heterozygote compared to either

homozygote?
– Reflects dominance
– Complete (heterozygote identical to either homozygote)
– No dominance (additive, heterozygote is intermediate)
– Partial (heterozygote more closely resembles one homozygote)
– Dominance influences how selection “sees” heterozygotes
– Affects rate of change across generations

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 Gene action: Additive vs. dominance
A2A2 A1A2 A1A1
additive
1-s 1-(1/2)s 1

A2A2 A1A2 A1A1

partial dominance
1-s 1-hs 1
A1A2
A2A2 A1A1
complete dominance

1-s 1

A2A2 A1A1 A1A2

overdominance
1-s2 1-s1 1
phenotype
Figure Credit: Falconer and Mackay. 1996. Used with permission of Pearson Education.

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 Dominance and rate of change

Figure Credit: Hartl. 2000. A primer of population genetics. Used with permission of Sinauer Associates.

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 Selection: Numerical example

Table Credit: White, T. L, W. T. Adams, and D. B. Neale. 2007. Forest genetics. CAB International, Wallingford, United Kingdom. Used with permission.

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 Natural selection: Fitness and selection
 Fitness: The relative contribution an individual (genotypic class)
makes to the gene pool of the next generation

www.pinegenome.org/ctgn Figure Credit: Nicholas Wheeler, Oregon State University

 What if selection is weak or absent?
 We’ve already seen that mutation can supply new variation that
selection may act upon

 Most mutations are deleterious and are lost, but rarely,

advantageous mutations can occur

 What about mutations that cause no effect either way?

 The neutral theory of evolution pertains to alleles that confer no

difference in relative fitness – as if selection is oblivious to them

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 Population genetics: A final concept
Linkage disequilibrium (LD, also called gametic phase disequilibrium)

 Conceptually – LD is a correlation in allelic state among loci

 Numerically
– Expected haplotype (gamete) frequency is the product of the two allele
frequencies, i.e. f(AB) = f(A) x f (B)
– If f(AB) = f(A) x f (B), then LD = 0
– If f(AB) ≠ f(A) x f (B), then LD ≠ 0

 LD may arise from factors such as

– Recent mutations
– Historical selection (hitchhiking effect)
– Population admixture

 Recombination causes LD to decay over generations

 LD plays a major role in association genetics

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 A numeric example of LD
 Determine allele frequencies

 Ask whether f(A) x f(B) = f(AB)

 Repeat for f(Ab), f(aB), and f(ab)

 Linkage disequilibrium (LD) reflects this difference

Gamete Type Gamete Frequency Gamete Type
(linked) (unlinked)
No LD Higher LD Lower LD
A B A B
0.42 0.60 0.55
A b A b
0.28 0.10 0.15
a B a B
0.18 -- 0.05
a b 0.12 0.30 0.25 a b

f(A) = 0.7 f(B) = 0.6 f(A) = 0.7 f(B) = 0.6

f(a) = 0.3 f(b) = 0.4 Allele Frequencies f(a) = 0.3 f(b) = 0.4

Image Credit: David Harry, Oregon State University

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 Some concluding remarks
 The central themes of population genetics remain
– How much genetic diversity is there?
– How is it distributed?
– How did it get that way?

 The foundation of population genetics, identifying and quantifying

genetic diversity, is no longer constrained by the lack of genetic
markers. We can now measure diversity in literally thousands of
genes simultaneously, and study how it is distributed

 Molecular population genetics

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 References cited
 Falconer, D. S., and T.F.C. Mackay. 1996. Introduction to Quantitative Genetics. 4th Ed.
Pearson Education (Longman Group Ltd.), Essex, England.

 Hamrick, J. L., and M.J.W. Godt. 1990. Allozyme diversity in plant species. p. 43-63. In Brown,
A.H.D., Clegg, M. T., Kahler, A. L., and B. S. Weir (ed.) Plant population genetics, breeding,
and genetic resources. Sinauer Associates, Sunderland, MA.

 Hartl, D. L. 2000. A primer of population genetics. Sinauer Associates, Sunderland, MA.

 Hartl, D. L., and E. W. Jones. 2001. Genetics: Analysis of genes and genomes, 5th edition.
Jones and Barlett, Sudbury, MA.

 Kimura, M. 1983. The neutral theory of molecular evolution. Cambridge University Press, New
York.

• White, T. L, W. T. Adams, and D. B. Neale. 2007. Forest genetics. CAB International,

Wallingford, United Kingdom. Available online at:
http://bookshop.cabi.org/?page=2633&pid=2043&site=191 (verified 26 May 2011).

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 External link
 Wikipedia contributors. 2011. Neutral theory of molecular evolution. Wikipedia, The Free
Encyclopedia. Available at:
http://en.wikipedia.org/w/index.php?title=Neutral_theory_of_molecular_evolution&oldid=421184
222 (verified 26 May, 2011).

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Thank You.
Conifer Translational Genomics Network
Coordinated Agricultural Project

www.pinegenome.org/ctgn